A combination of anatomical and physiological approaches will be used to characterize the responses of isolated human coronary arterial smooth muscle obtained mainly from autopsies as soon as possible after death. The anatomical studies will use histochemical and ultrastructural methods to build up a detailed picture of the innervation of the vessel, the arrangement of the muscle bundles within the wall and the size, shape, interrelationships and contacts of the individual smooth muscle cells. The frequency of nexuses will be assessed. Variations in innervation and ultrastructure at different levels of the coronary tree will be determined. In parallel with these studies the spontaneous mechanical activity of human coronary smooth muscle will be assessed in isolated rings in Krebs-bicarbonate solution and in segments perfused with this solution and with plasma and blood. The responses to neural stimulation and to vasoconstrictors such as catecholamines and ergonovine will be determined as will the effects of vasodilators such as nitrates, nitroprusside and verapamil. The role of prostaglandins in spontaneous and induced contractions will be studied. Electrophysiological techniques using intracellular glass microelectrodes will be used to determine the nature of the electrical membrane events which underly spontaneous and induced phasic contractions. A major goal will be to determine the ionic dependence of the electrical and mechanical changes and the source of the activator calcium. Animal models resembling the human in their anatomy and physiology will be sought. These studies are directed to obtaining basic data necessary for the understanding of coronary arterial spasm.